Dr. W. Taylor Kimberly is a Neurocritical Care and Stroke Neurologist at Massachusetts General Hospital (MGH), whose goal is to become an independent investigator with expertise in metabolomics, insulin resistance and to define its contribution to stroke and other cerebrovascular diseases. His career development plan leverages the resources of a world-class environment by bringing together an outstanding team of investigators centered at a leading academic institution in Boston, Massachusetts General Hospital. Dr. Kimberly has already obtained preliminary results demonstrating the feasibility of research plan that uses a novel metabolomic platform that can analyze more than 300 key metabolites at the same time. Under the mentorship of Dr. Robert Gerszten, and co-Mentors Dr. Greg Sorensen and Dr. Jose Florez, Dr. Kimberly proposes: 1) To determine whether branched chain amino acids are altered in the setting of stroke, 2) To determine whether hyperglycemia of stroke influences the way branched chain amino acids (valine, isoleucine and leucine) are altered, and 3) To prospectively investigate whether glucose metabolism and branched chain amino acid alterations will predict neurological outcomes. The overall goal is to elucidate the mechanisms that underlie hyperglycemia in acute stroke and to determine how this leads to worse neurological outcomes. Bringing together cutting-edge technology and a team with relevant expertise, this project will open new avenues for treatment in stroke. This well-defined patient-oriented research proposal, in concert with mentorship and a structured didactic curriculum, will provide Dr. Kimberly with the skills that are essential for him to develop an independent career in cerebrovascular research at the cutting edge of science. PUBLIC HEALTH RELEVANCE: Despite modern advances in prevention and treatment, stroke remains the leading cause of adult disability and the second leading cause of death worldwide. Dr. Kimberly's proposed career development plan has outstanding potential to advance our knowledge of the interaction between metabolism and ischemic stroke, which is a crucial step towards the discovery of novel treatment strategies.